Studies were performed in vivo to determine the ability of the antiestrogen U-11, 100A (UA) [nafoxidine hydrochloride] to modulate the binding of the estrogen receptor [ER] to uterine nuclei. UA (100 .mu.g) injected at 30, 60 or 120 min into immature female rats arrested the rapid estradiol receptor complex (ERC) clearance from the nuclei after the 1 h accumulation which normally occurs after a single 5 .mu.g injection of 17.beta.-estradiol (E2). The UA receptor complex accumulated in the nuclei and was retained for at least 48 h. As there is no indication of any significant replenishment of the cytoplasmic ER within the first 12 h after a UA (100 .mu.g) injection or after an E2 (5 .mu.g) injection followed by a subsequent UA (100 .mu.g) injection at 30, 60 or 120 min, the UA appears to be recapturing ER initially translocated to the nuclei. By 24 h after a UA injection there is replenishment of cytoplasmic ER and subsequent E2 injections at this time will cause the nuclear translocation of ERC and maximal formation of KCl-resistant ERC (about 0.22 pmol/uterus). After a single injection of E2 (5 .mu.g) there is a period of a few hours in which a subsequent injection of E2 is unable to induce the nuclear accumulation of ERC. Only when there is sufficient replenishment of cytoplasmic ER can a reaccumulation of the nuclear ERC occur with subsequent E2 injections. The formation of the KCl-resistant form of the ERC by a single injection of E2 (5 .mu.g) appears by 15 min, and is maximal at 30 min, remaining at this level for approximately 2 h with a gradual decrease by 6 h. This pattern could also be modified by antiestrogens. UA (100 .mu.g) injected 30 or 60 min after E2 (5 .mu.g) resulted in the immediate loss of the KCl-resistant ERC. The antiestrogen may be capable of exchanging with E2 on the salt-resistant nuclear ER causing conversion of the ER from a KCl-resistant form to a KCl-extractable form.